Background: Acyl-coenzyme A cholesterol acyltransferase (ACAT) is a membrane-binding enzyme, which localizes in the endoplasmic reticulum. ACAT2 can promote the progression of colon cancer, but its efficacy in lung adenocarcinoma(LUAD) is still not sure. Method: ACAT2 expression analysis was performed by TIMER2.0 database. GEPIA database was utilized to analyse co-relations between expression of ACAT2 and pathological stage of tumor. Kaplan-Meier analysis was analyzed its potential in clinical prognosis. CancerSEA database analysed correlations between expression of ACAT2 and functional status of different tumor displayed as a heatmap. The molecule interaction network analysis performed by the STRING tool. Results: ACAT2 was upregulated in patients with LUAD, and high expression of ACAT2 had a poor DFS and OS. Cox regression analysis indicated that the poor outcomes might be related to the tumour stage, nodal stage, distant metastatic stage. ACAT2 participated in biological process of cell cycle, DNA repair, DNA damage, proliferation. Enrichment pathway analysis showed four ACAT2-correlated genes, ACOX1, EHHADH, OXCT1, DLAT. Conclusion: ACAT2 might be a novel predictive biomarker and treated target.

Dear Editor, Following the publication of our preliminary investigation on down-regulated miRs in gastric cancers 1, we completed the analyses focusing on the 4 upregulated miRs (miR21, miR135b, miR196a, miR196b) on the same cohort of 117 non-cardial gastric cancer patients. The investigation was carried with the same identical experimental design and statistical analyses, as previously described. 1

In this paper, we discuss how to synthesize stabilizing Model Predictive Control (MPC) algorithms based on convexly parameterized Integral Quadratic Constraints (IQCs), with the aid of general multipliers. Specifically, we consider Lur’e systems subject to sector-bounded and slope-restricted nonlinearities. As the main novelty, we introduce point-wise IQCs with storage in order to accordingly generate the MPC terminal ingredients, thus enabling closed-loop stability, strict dissipativity with regard to the nonlinear feedback, and recursive feasibility of the optimization. Specifically, we consider formulations involving both static and dynamic multipliers, and provide corresponding algorithms for the synthesis procedures. The major benefit of the proposed approach resides in the flexibility of the IQC framework, which is capable to deal with many classes of uncertainties and nonlinearities. Moreover, for the considered class of nonlinearities, our method yields larger regions of attraction of the synthesized predictive controllers (with reduced conservatism) if compared to the standard approach to deal with sector constraints from the literature.

The researcher will introduce the way of effective liquid chromatography tandem mass spectrometric method (HPLC-MS) which is quick, sensitive, and alternative to determine the (E)-3-(3,4-dihydroxyphenyl) -2-(3-(3,4-dihydroxyphenyl)acrylamido)propanoic acid (A1) and rosmarinic acid (RA) of the plasma in rats. The analyses were divided into a C18 column (1.9 μm, 2.1 mm × 100 mm) with a security guard C18 column (5 μm, 2.1 mm × 10 mm) and a triple-quadrupole mass spectrometry with an electrospray ionization (ESI) ion-source generates ions. With Pseudoephedrine hydrochloride being a standard, the sample pretreatment is relevant to the one-step protein precipitation with isopropanol: ethyl acetate (v/v, 20:80). This method presented a linear relationship within ranges of the concentration of 5–750 ng/ml for RA and A1. Relative standard deviations (RSD) in daily courses stood less than 15% and the relative errors (RE) registered within 15%. The means adopted in this research makes the RA’s and A1’s unambiguous quantification and identification and in vivo possible. And this study can be the first one to focus on determining the A1 and RA of rat plasma with administration orally. The results served as a significant basis to evaluate the medicine’s applications in the clinic.

Background and Objective: Pulse diagnosis is the most characteristic method of diagnosis in traditional Chinese medicine and contains a wealth of pathophysiological information. This study aimed to investigate the acoustic characteristics of the pulses of pregnant women in mid- to late-term pregnancy (pregnant women) and relatively healthy women without pregnancy (non-pregnant women). The pulse of the wrist was divided into three parts: the Cun, Bar, and Cubit, each of which was divided vertically into five layers. The perspective of the acoustic factors in the pulse was analyzed to compare the differences in the acoustic pulse of pregnant and non-pregnant women. Methods: The acoustic characteristics of the pulse were analyzed using wavelet analysis and empirical modal decomposition by combining multi-scale entropy and Shannon entropy, and the differences between the two groups were examined. Receiver operating characteristic (ROC) curves were plotted to judge the sensitivity and accuracy of the acoustic wave characteristics for the preliminary diagnosis of pregnancy in women. Results: The parameters of the third and fourth layers of the Cubit pulse in pregnant women were significantly different to those of non-pregnant women. The multi-scale entropy, Shannon entropy values, energy, and acoustic wave amplitude of the pulses of pregnant women were higher than those of non-pregnant women, which indicates that pregnant women had more complex waveform. The acoustic wave characteristics of pregnant women mainly manifested in the EG and IJ segments of the third layer of the Cubit pulse, and IJ segment of the fourth layer of the Cubit pulse

The liver is known for its remarkable regenerative capacity to restore liver architecture and re-establish specific functions after various types of liver injury. However, in patients with end-stage liver disease, the regenerative capacity is inhibited and liver transplantation is the only option. Considering the limitations of liver transplantation and the prevalence of liver regeneration in liver injury, promoting liver regeneration is suggested as an effective strategy for treating patients with liver disease. Liver regeneration is a complex process involving the regulation of cytokines, growth factors, and metabolic signals. Traditional Chinese medicine (TCM) has been practiced for thousands of years due to its comprehensive intervention advantages with multi-component and multi-pathway. Recent studies have described that TCM can effectively promote liver regeneration. In this review, we provide an overview of the molecular mechanisms involved in the process and regulation of liver regeneration. Subsequently, we first summarize the pro-regenerative activity and mechanism of TCM formulas, extracts and active ingredients, which reveal the potential of TCM in promoting liver regeneration and provide reasonable evidence for TCM in the prevention and treatment of patients with clinical liver disease.

Cluster Subcutaneous Allergen Immunotherapy as a Sustainable Practice Towards Net Zero HealthcareAlicia Domínguez Estirado1, Inmaculada Sánchez-Machín2,3, Paloma Poza-Guedes2,4 and Ruperto González-Pérez2,4

A fractional flow formulation is proposed to model two-phase flow in heterogenous porous media in the case of low interfacial tension. The proposed formulation overcomes the limitations of the fractional flow approach that arise from saturation discontinuity. The total velocity is calculated with two terms. A total mobility term multiplied by the non-wetting phase potential which is a smooth term over the computational domain. The second term is the buoyancy term that represents the density contrast between the two phases. The proposed formulation is verified with the Buckely--Leverett analytical solution. Two other numerical examples are presented in 2D and in 3D. The examples show the applicability of the model in anisotropic and in heterogenous porous media and demonstrate the low mesh dependency of the model.

The hydrological cycle, also known as the water cycle, is a critical component of the Earth's ecosystem, regulating the planet's temperature and providing water for plants and animals to survive. However, human activities such as excessive water usage can disrupt this cycle. In this article we investigated the key variables and feedback loops that comprise the hydrological cycle system and developed a dynamic model using system dynamics method. By developing this dynamic model, this article aims to provide a deeper understanding of the underlying mechanisms driving changes in the hydrological cycle and how they are interconnected. This knowledge can aid in the sustainable use and protection of water resources.

After a drug is granted a marketing license, its post-marketing surveillance is evaluated to ensure that it is continuously monitored for undesirable effects. This monitoring is achieved through an effective Pharmacovigilance system. In our review, we discuss the Pharmacovigilance systems of Europe, the United States, and India, along with several examples of effective Pharmacovigilance strategies, such as the Tracleer® Access Programme and Tracleer® Excellence programs for Bosentan, Merck’s Worldwide Adverse Experience System, the European and United States Varicella Zoster Virus Identification Programs for Varivax, the Siddha Initiative for Documentation of Drug Adverse Reaction, an android mobile app for AYUSH Pharmacovigilance, and the Global Pharmacovigilance Database by Sanofi Pasteur. This report demonstrates the importance of post-marketing surveillance in detecting rare adverse experiences that may go unnoticed during clinical trials. It also emphasizes the significance of highlighting the field of Pharmacovigilance to improve patient safety and offer them the best possible quality of life.

Nowadays, educational institutions gather and save a vast amount of data, including records of student enrollment, attendance, and exam outcomes. Such data can be mined to produce interesting information that is helpful to those who handle it. New ways to assess e-pedagogical learning's efficiency are required due to the increased interest in it as a crucial teaching and learning process. This paper offers a data mining research scenario for the next 20 years where the setting is e-learning, and the key topic is the assessment component, which is seen as a latent issue in this environment. Our objective is to present an understudied review of educational data mining research on the teaching and learning process while taking the viewpoint of education into consideration.

ion The rise of new areas of information technology and the ever-increasing significance of interactive features in e-learning environments have inspired adaptive e-learning. Although researchers have been working incessantly for the past 20 years to include intelligent and adaptive elements in e-learning software, these features are typically ad hoc and only serve partial views. Due to the lack of a unified structure, framework, or standard, many adaptive e-learning perspectives frequently have characteristics that are repeated and overlapped with one another. The main elements of adaptive e-learning are identified in this paper, along with their unique viewpoints. We present a succinct overview of the approaches in use for the various adaptive aspects of these components. Additionally, we also present a hierarchical structure of several adaptive e-learning components, which serves as a framework for this review study.

Purpose: Reducing initial exposure of “opioid naïve” patients to opioids is a public health priority. Identifying opioid naïve patients is difficult, as numerous definitions are used. The objective is to summarize current definitions and evaluate their impact on opioid naïve measures in Alberta. Methods: Using dispense data (2017-2021) and definitions guided by a scoping review, we determined the number of “opioid naïve” patients using descriptive analyses. Three definitions were identified: 1) no opioid use within the previous 30 days/6 months/1 year, based on dispensation date; 2) definition 1, based on dispensation date plus days of supply; 3) exclusion of codeine from definitions 1 and 2. Results: Of over a dozen definitions of opioid naïve identified in the scoping review, most used an ‘opioid free’ period (commonly 30 days/6 months/1 year). Other definitions included “availability of drug” based on days of supply and/or excluded certain opioid products. Approximately 36.4% of Albertans (n=1,551,075) had an opioid dispensation in 2017-2021. The average age was 46.6±18.8 and 52.8% were female. Results were most affected by the “opioid free” period, with 97.4%, 83.2% and 65.6% being classified as opioid naïve using time windows from definition 1. Definitions 2 and 3 did not materially change the results. Conclusions: The most convenient definition for “opioid naïve” was definition 1 using a 1-year window, which aligns with the Canadian Institutes for Health Information definition. Irrespective of definition used, a large proportion of opioid users would be considered opioid naïve despite initiatives to curb opioid prescription in Alberta.

Background Based on previous reports of disparities in financial burden following cancer, this study aims to characterize mechanisms of disparities experienced by caregivers of children with cancer, including the impact of work flexibility and social support. Methods Cross-sectional survey (in English or Spanish) of caregivers of children with cancer that assessed household material hardship (HMH), financial toxicity and income change. Results Of 156 caregivers surveyed, 32% were Hispanic and 32% were low income. Hispanic caregivers were more likely to report HMH and financial toxicity compared to non-Hispanic White and Asian (HMH 57% v. 21% v. 19%, p<0.001; financial toxicity 73% v. 52% v. 53%, p=0.07). Low and middle income caregivers were more likely to experience HMH and financial toxicity compared to high income (HMH: 68% low v. 38% middle v 8.7% high, p<0.001; financial toxicity: 81% v. 68% v. 44%, p<0.001). All income categories demonstrated significant increases in HMH one year after diagnosis. Seventeen percent reported >40% income loss, more of whom were low income than high income (27% v. 12%, p=0.20). Work flexibility and social support were associated with income and financial toxicity. Conclusion HMH, financial toxicity, and income loss are prevalent after a child’s cancer diagnosis, suggesting that screening should be incorporated into routine care. This financial burden disproportionately affects low income and Hispanic caregivers. Further research is underway to understand how safety net services are utilized by families, how best to support families with HMH, and how the financial burden of cancer has been impacted by COVID-19.

Background: In our earlier published outcomes of children with acute lymphoblastic leukemia (ALL) at Moi Teaching and Referral Hospital in Kenya (MTRH), we showed low event-free survival (EFS) with high induction mortality and abandonment. Based on this observation, the team focused on strategies to reduce both causes of poor outcomes. Intervention: We dropped doxorubicin from induction therapy as the supply of L-asparaginase became reliable, improved social and financial support for insurance coverage and transportation, promptly initiated empirical antibiotics during episodes of febrile neutropenia, and enhanced the availability of blood products. Objective: Our study compared childhood ALL outcomes before (2010-2016) and after (2017-2020) modification of induction therapy, with improved social and financial support and supportive care. Methods: We reviewed the medical records of 123 children with ALL between 2017 to 2020. Their treatment results were collected and compared to those of 136 children before the (2010-2016) modification of induction therapy, with improved social and financial support. Results: Three-year EFS estimates improved from 18.2% to 40.7%. Relapse or progressive disease decreased from 26% to 16%, and abandonment from 24% to 14%. Deaths and survival through induction did not change significantly between the two periods. Children between 1-9 years and those with white blood cell (WBC) count <50x10 9/L had better EFS. Conclusions: Treatment abandonment and relapse decreased, and EFS increased significantly. However, strategies to improve early diagnosis and supportive care are needed to reduce induction mortality. In addition, enhanced parental education and continuous counseling are required to minimize treatment abandonment further.

Introduction: Parkinson’s disease (PD) is a multisystem disease, involving several brain structures. fMRI studies reported abnormal functional connectivity (FC) in PD. EEG is an accessible method to evaluate cortical activity, which may be used to estimate FC. For this aim, we analyzed differences in FC between patients at early stages of PD and healthy controls (HC) using high-density EEG (HD-EEG). Methods: We enrolled 20 early-stage PD patients and 19 age-matched HC. Data were recorded with a 64-channels HD-EEG system. A source-reconstruction method was used to identify brain-region activity. FC was calculated using a weighted phase-lag index in θ-α-β bands. Network-based statistic was used to compare FC between PD and HC. Results: No statistical-significant differences were observed in spectral analysis between groups. PD patients showed a hypoconnected network in α-band primarily composed by frontal lobe, associated with a hyperconnected network in β band, including frontal, sensorimotor, limbic and temporal areas. Moreover, correlation between β FC in sensorimotor areas and PD motor impairment was found (r = 0.80, p = 0.003). Conclusion: HD-EEG revealed FC alterations since early stages of PD, as a tool complementary to fMRI, and it could be a useful early or even preclinical diagnostic marker of disease.

With inspiration of the definition of Bernstein basis functions and their recurrence relation, in this paper we give construction of new concept so-called Bernstein-based words. By classifying these Bernstein-based words as first and second kind, we investigate their some fundamental properties involving periodicity and symmetricity. Providing schematic algorithms based on tree diagrams, we also illustrate the construction of the Bernstein-based words. Moreover, we give computational implementations of Bernstein-based words in the Wol-fram Language. By executing these implementations, we present some tables of Bernstein-based words and their decimal equivalents. In addition, we present black-white and 4-colored patterns arising from the Bernstein-based words with their potential applications. We also give some finite sums and generating functions for the lengths of the Bernstein-based words. We show that these functions are of relationships with the Catalan numbers, the centered m-gonal numbers, the Laguerre polynomials, certain finite sums, and hypergeometric functions. We also raise some open questions and provide some comments on our results. Finally, we investigate relations between the slopes of the Bernstein-based words and the Farey fractions.

Abstract Objective: This study aimed to identify the association between resilience and social participation, to clarify sub-trajectory of social participation of stroke survivors with different levels of resilience, and to describe stroke survivors with different levels of resilience how to re-integrate into society. Background: Stroke can be considered as a catastrophe which severely affects the social participation of the survivors. Resilience, a buffer against stress and adverse event, its protective effect and mechanism on social participation has not been established. Design: A longitudinal study. The study will be conducted in November 2022 and will continue until January 2024. Methods: First-episode stroke survivors will be recruited from three hospitals, when they had stable vital signs and about to discharge. Follow-up assessments will be performed in 1, 3, 6, 9, and 12 months after stroke survivors’ onset. A multilevel model will be used to explore the relationship between resilience and social participation. Growth Mixture Modeling (GMM) will be used to analyze potential heterogenicity trajectory of social participation. Inductive content analysis will be applied to describe how participants with different levels of resilience return to social life. Conclusions: Our study seeks to examine the association between resilience and social participation and provide a potential perspective of hierarchical intervention programme in enhancing social participation in stroke survivors.

Background: Primary malignant lymphomas (PHML) of the larynx are exceptional. Case: A 43-year-old man presented with dysphonia and pulmonary aspiration. The physical examination found bilateral cervical lymph nodes and the pan endoscopy revealed a bleeding budding tumor of the epiglottis. The head and neck scan showed a mass arising from the epiglottis and invading the vallecules, the right aryepiglottic fold, the two vocal cords and the anterior commissure with bilateral cervical lymph nodes. The patient inderwent a chemotherapy, followed by an irradiation of the involved nodal fields and the initial laryngeal tumor. At a follow-up time of 3.5 years, the patient remains in disease complete remission. Conclusion: We report the first case of laryngeal PHML. Given the lack of recommendations for this extremely rare type of tumor. The prognosis, even if it seems to be good, it is difficult to specify whether it matches that of other localizations or not. Keywords: Laryngeal Tumors, Malignant Hodgkin Lymphoma, head and neck, Chemotherapy, Radiotherapy

Our ability to merge information from different senses into a unified percept is a crucial perceptual process for efficient interaction with our multisensory environment. Yet, the developmental process underlying how the brain implements multisensory integration remains poorly known. This cross-sectional study aims to characterize the developmental patterns of audiovisual events in 131 individuals aged 3 months to 30 years. Electroencephalography (EEG) was recorded during a passive task, including audiovisual, auditory, and visual stimulations. Different developmental patterns are seen for the audiovisual, auditory, and visual responses, with the visual and audiovisual responses reaching maturity between 11 and 14 years old and the auditory response reaching maturity a few years later, between 15 and 17 years old. Topographic distributions reveal distinct audiovisual developmental patterns across age groups. Specifically, from 3 months to 7 years old, audiovisual interaction emerges in the left temporo-parietal regions and reaches the medial frontal area between 8 and 10 years old, followed by a mature fronto-central pattern from 11 years old. Our results show that response to the bimodal events is a long developmental process that emerges during childhood and continues to develop during adolescence.

To systematically evaluate efficacy of regimens containing arsenic trioxide (ATO) for the patients with myelodysplastic syndrome and explore optimal combination. Randomized clinical trials about regimens containing ATO were retrieved from China National Knowledge Infrastructure, Embase, PubMed et al. With odds ratio as the effect size, network meta-analysis and component network meta-analysis was conducted by utilization of R and ‘netmeta’ package, after study selection, quality assessment and data extraction. As the result, thirty-eight RCTs were included with a total of 2089 patients, including 1257 treated by ATO containing regimen. With support therapy alone as reference, insignificant inconsistency and heterogeneity was observed. Although NMA did not demonstrate better efficacy of ATO alone, result of CNMA indicated that ATO was effective in improvement of ORR [OR=2.03(1.56, 2.64)] and CR [OR =1.66(1.24, 2.22)]. Five ATO-containing regimens reported could effectively improve ORR, some of them benefit in CR or HI as well. ATO+T+TCM was regarded as the optimal combination, which improved both ORR [OR=3.11(2.08, 4.66)], CR [OR=7.09(1.53, 32.82)] and HI [OR=2.02(1.24, 3.27)] in theory. ATO did not increase the risk of common adverse events compared to supportive therapy [(OR=0.90(0.67, 1.21)]. In conclusion, ATO is an effective and well tolerant option for patients with myelodysplastic syndrome.

The union territories of Jammu and Kashmir and Ladakh are energy-undernourished union territories though they are hallowed with immense solar energy potential for thermal power generation and photovoltaic. Advancing and revitalizing resource gauging of all renewable energy sources is essential in the present layout where there has been a drastic scarcity of energy in the union territories. Among all Renewable Energy sources, solar energy can also play a key role in curtailing the energy crisis in the union territories of J&K and Ladakh and can be useful in providing energy in the future. It can dispense firm energy supply with additional income to the union territories of J&K and Ladakh and shall provoke employment in the union territories of J&K and Ladakh. This paper sheds light on how solar energy can lighten the energy demand to curtail the energy crisis in the union territories of Jammu and Kashmir, and Ladakh based on Clean and green energy. The data obtained from National Renewable Energy Laboratory (NREL) proclaim that Jammu and Kashmir, and Ladakh are provided with about 5.3 kWh/m 2 /day of mean direct normal irradiance (DNI) and 5.2 kWh/m 2 /day of mean global horizontal irradiance (GHI). Both DNI and GHI can be turned into good accounts for solar thermal power generation and photovoltaic power generation.

Consumption of foods contaminated with aflatoxin B1 (AFB1) is a recognized risk factor for developing hepatocellular carcinomas (HCCs). The mutational signature of AFB1 is characterized by high frequency G > T transversions in a limited subset of trinucleotide sequences. The 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxyaflatoxin B1 (AFB1-FapyGua) has been implicated as the primary DNA lesion responsible for AFB1-induced mutations. This study evaluated the mutagenic potential of AFB1-FapyGua in four contexts, including hot- and cold-spot sequences as apparent in the mutational signature. Vectors containing AFB1-FapyGua were replicated in primate cells and the products of replication were isolated and sequenced. Regardless of the sequence context, AFB1-FapyGua caused base substitutions at frequencies of ~ 80-90%, with G > T transversions being most common. Spectra of mutations were only slightly modulated by the sequence context. These data suggest that mechanism(s) defining sequence context-dependent distribution of AFB1-induced mutations likely operates prior to replication.

Landlocking of diadromous fish in freshwater systems can have significant genomic consequences. For instance, the loss of the migratory life stage can dramatically reduce gene flow across populations, leading to increased genetic structuring, and stronger effects of local adaptation. These genomic consequences have been well-studied in some mainland systems, but the evolutionary impacts of landlocking in island ecosystems are largely unknown. In this study, we used a genotyping-by-sequencing (GBS) approach to examine the evolutionary history of landlocking in common smelt (Retropinna retropinna) on Chatham Island, a small isolated oceanic island 650 km southeast of mainland New Zealand. We examined the relationship among the Chatham Island and mainland smelt, and used coalescent analyses to test the number and timing of landlocking events on Chatham Island. Our genomic analysis, based on 21,135 SNPs across 169 individuals, revealed that the Chatham Island smelt were genomically distinct from the mainland New Zealand fish, consistent with a single ancestral colonisation event of Chatham Island in the Pleistocene. Significant genetic structure was also evident within the Chatham Island smelt, with a diadromous Chatham Island smelt group, along with three geographically structured landlocked groups. Coalescent demographic analysis supported three independent landlocking events, with this loss of diadromy significantly pre-dating human colonisation. Our results illustrate how landlocking of diadromous fish can occur repeatedly across a narrow spatial scale, and highlight a unique system to study the genomic basis of repeated adaptation.